Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis最新文献

{"title":"Thrombotic thrombocytopenic purpura associated with acalculous cholecystitis masquerading as immune thrombocytopenia.","authors":"Kavya Balusu, Purva Shah, Nagesh Jadhav, Mehul Patel","doi":"10.1097/MBC.0000000000001432","DOIUrl":"10.1097/MBC.0000000000001432","url":null,"abstract":"<p><p>Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening condition characterized by thrombocytopenia, microangiopathic haemolytic anaemia, and end-organ ischemia. Association of TTP with acute cholecystitis is rare, with only two cases reported in literature. We report the third case of TTP associated with acute cholecystitis in an African-American female with systemic lupus erythematosus (SLE). She presented with fever and abdominal pain; laboratory testing revealed acute on chronic thrombocytopenia, and imaging confirmed acute acalculous cholecystitis. This initially led to a misdiagnosis of immune thrombocytopenia (ITP), and she was treated with antibiotics, intravenous immunoglobulin, and steroids without improvement. She subsequently developed neurological symptoms with laboratory evidence of haemolysis raising a concern for thrombotic microangiopathy. Emergent plasmapheresis was initiated for suspected TTP, resulting in improvement of her symptoms. Low ADAMTS13 activity subsequently confirmed the diagnosis. This case highlights the importance of recognizing atypical presentations of TTP to initiate prompt life-saving treatment.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"233-236"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune thrombotic thrombocytopenic purpura complicated with Evans syndrome: a case report and literature review.","authors":"Maolan Wu","doi":"10.1097/MBC.0000000000001426","DOIUrl":"10.1097/MBC.0000000000001426","url":null,"abstract":"<p><p>The co-occurrence of immune-mediated thrombotic thrombocytopenic purpura (iTTP) and Evans syndrome (ES) is clinically rare. This article reports the rare case of a 73-year-old male patient with simultaneous iTTP and ES. He was admitted due to \"dry cough for 1 month, fever for half a month, and impaired consciousness for 3 days.\" Initial symptomatic treatments included anticoagulation and correction of heart failure, but his hemoglobin and platelet counts declined progressively. He was later diagnosed with iTTP following consultation with the hematology department and laboratory tests. His platelet count and lactate dehydrogenase levels improved after plasma exchange plus corticosteroid therapy for 3 days; however, the family ultimately opted to discontinue treatment due to progressive multiple organ dysfunction. This report discusses the clinical and pathological mechanisms and therapeutic challenges associated with coexisting iTTP and ES, highlighting the importance of multidisciplinary collaboration and individualized diagnosis and treatment.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"228-232"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes type 2: magnitudes of agonist-evoked platelet activity markers in vitro demonstrate a substantial individual dependence.","authors":"Maria Edvardsson, Magnus Oweling, Petter Järemo","doi":"10.1097/MBC.0000000000001431","DOIUrl":"10.1097/MBC.0000000000001431","url":null,"abstract":"<p><p>In type 2 diabetes (T2DM), of the pathways and magnitudes of whole blood agonist-evoked responses, that is, platelet reactivity is not well understood. This study aimed to identify mechanisms regulating platelet reactivity in T2DM. The study included 35 individuals with T2DM. A flow cytometer analyzed whole blood agonist-evoked [α-thrombin (10 μmol/l) (α-thr), collagen (0.15 μg/ml) (coll), ADP (5 μmol/l)] surface phosphatidylserine (annexin V) expressions, fibrinogen receptor activities (PAC-1), and lysosomal exocytosis (LAMP-1) (all fluorescence intensities of normal-sized platelets). The correlation coefficient ( r ) compared induced activity markers for each agonist and agonist variations of platelet reactivity. Collagen-evoked and ADP-evoked annexin responses were inversely associated with PAC-1 (coll: r  = -0.6, ADP: r  = -0.7). Additionally, after provocation, annexin V and LAMP-1 were related contrariwise (all agonists: r  = -0.5). Agonist-induced PAC-1 correlated with LAMP-1 expressions (α-thr: r  = 0.5, coll: r  = 0.6, ADP: r  = 0.7). The study demonstrated that induced annexin V was closely associated (α-thr vs. coll: r  = 0.9, α-thr vs. ADP: r  = 0.7, coll vs. ADP: r  = 0.9). PAC-1 (α-thr vs. coll: r  = 0.8, α-thr vs. ADP: r  = 1.0, coll vs. ADP: r  = 0.8) and LAMP-1 (α-thr vs. coll: r  = 0.7, α-thr vs. ADP: r  = 0.8, coll vs. ADP: r  = 0.5) displayed similar relationships. The magnitudes of agonist-evoked reactions in vitro are associated, and the agonist category proved less significant for regulating agonist-induced activity. Close inverse correlations between agonist-evoked annexin V and both PAC-1 and LAMP-1 suggest that procoagulant reactions after provocation directed platelet activity. Thus, reactivity is regulated by platelet characteristics connected to the T2DM individuals.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"178-183"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between plasma homocysteine, vitamin B12, and folic acid levels with thrombotic diseases in Syrian patients.","authors":"Mhd Hasan Alkattan, Ruba Abdul Rahman Sharaf, Kenda Jawich, Rana Habeeb","doi":"10.1097/MBC.0000000000001427","DOIUrl":"10.1097/MBC.0000000000001427","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the relationship between plasma homocysteine, vitamin B12, and folic acid in Syrian patients with thrombotic diseases.</p><p><strong>Methods: </strong>We conducted a case-control study on patients with hyperhomocysteinemia associated with a thrombotic disease at the National University Hospital of Damascus, Syria, comprising 133 thrombosis patients (84 males, 49 females; aged 20-80 years) and 39 matched healthy controls. Vitamin B12 and folic acid profiles were analyzed, and homocysteine ≥15 μmol/l was considered as hyperhomocysteinemia.</p><p><strong>Results: </strong>Patients with thrombosis exhibited significantly higher levels of homocysteine compared to controls (38.93 ± 19.91 μmol/l versus 8.13 ± 2.42 μmol/l, respectively, P < 0.001). Additionally, they had lower levels of vitamin B12, with values of 159.19 ± 57.66 pg/ml compared to 521.26 ± 58.08 pg/ml in controls ( P < 0.001), and they had lower levels of folic acid compared to controls (5.14 ± 4.07 ng/ml versus 11.33 ± 2.17 ng/ml, respectively, P < 0.001). Moreover, hyperhomocysteinemia was the single vascular risk factor retrieved in 21.1% (28/133) of patients, with no other identified conventional risk factors.</p><p><strong>Conclusion: </strong>This study concludes that hyperhomocysteinemia is considered a strong and independent risk factor for thrombotic diseases and is strongly associated with vitamin B12 and folic acid deficiencies.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"198-206"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TEG 6s thrombelastography versus conventional coagulation assays in infants and toddlers during craniosynostosis surgery: a prospective observational clinical study.","authors":"Frank Fideler, Franziska Beck, You-Shan Feng, Berthold Drexler, Harry Magunia, Martin U Schuhmann, Peter Rosenberger, Andreas Straub","doi":"10.1097/MBC.0000000000001425","DOIUrl":"10.1097/MBC.0000000000001425","url":null,"abstract":"<p><p>Craniosynostosis surgery is associated with severe diffuse bleeding, which can result in a significant coagulopathy. The aim of this study was to compare Thrombelastograph Coagulation Analyzer TEG 6s parameters and the time required for result availability with conventional coagulation parameters (CCP) during pediatric craniosynostosis surgery. In this prospective clinical observational study, 29 infants and toddlers (median age 6 months, median weight 8.5 kg) undergoing craniosynostosis surgery were enrolled. Blood was sampled preoperatively and perioperatively. Samples were analyzed by TEG 6s and CCP [prothrombin time (PT) (for analysis of quick time/INR), aPTT, fibrinogen, factor XIII, and antithrombin III]. The TEG 6s parameters (reaction time ' R ', coagulation time ' K ', maximum amplitude 'MA') and CCP were related using linear regression analyses. The required turnaround times for both methods (TEG 6s and CCP) were recorded as medians and interquartile ranges [IQR]. Highest R2 values were obtained for the CK-R-aPTT relationship ( R2  = 0.448), for the CK-MA-fibrinogen relationship ( R2  = 0.47) and for the CK-K-aPTT relationship ( R2  = 0.631). Initial availability was after 30 [9.1-14.1] min for CCP and after 16.1 min [9.1-14.1] for TEG 6s. Linear relationships between TEG 6s and CCP are rather low. This is best explained by the fact that TEG 6s and CCP do not measure identical coagulatory substrates and dynamics. However, regarding the TEG 6s-related time advantage compared to CCP and the possibility to monitor coagulation dynamics including fibrinolysis the TEG 6s is well-suited to guiding coagulation management in children undergoing craniosynostosis surgery.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"168-177"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular pathogenesis of coexisting type 1 von Willebrand disease caused by gene conversion and severe hemophilia a with F8 intron 22 inversion in a Chinese patient.","authors":"Ziyan Wei, Yayun Ling, Yulin Xu, Jinxiong Jiang, Xiaoying Lv, Xiaoyun Su, Yanxi Zhou, Yu He, Fuyong Zhang","doi":"10.1097/MBC.0000000000001435","DOIUrl":"10.1097/MBC.0000000000001435","url":null,"abstract":"<p><p>To identify and characterize a case of coexisting von Willebrand disease (VWD) and hemophilia A, and elucidate the underlying genetic mutations and molecular mechanisms. Coagulation function, VWF activity (VWF:Act), and VWF antigen (VWF:Ag) were measured using a fully automatic coagulometer. FVIII recovery rate and half-life were assessed with PKSolver, and FVIII inhibitors were detected using the Bethesda assay. VWF multimer analysis was performed to clarify the clinical phenotype. Genetic analysis included next-generation sequencing of the VWF gene and multiplex ligation-dependent probe amplification (MLPA) for F8 gene inversions. Bioinformatics tools (ClustalX-2.1, SWISS-MODEL, PyMOL) were used to analyze mutation conservation and impact on protein structure. Laboratory findings revealed severe hemophilia A (FVIII:C 0.5%) and mild type-1 VWD. FVIII recovery was 67.5% with a 4.9 h half-life, and no inhibitors were detected. Genotyping revealed F8 intron 22 inversion, two VWF gene conversion variants (p.V1229G; p.N1231T) inherited maternally, and a paternal missense variant (p.R2118W). In-silico analysis showed loss of the Gly1229-Thr1231 hydrogen bond destabilizing the D'D3 domain, whereas p.R2118W preserved hydrogen bonding in the D4 domain, supporting mild structural impact. We confirmed a case of severe hemophilia A coexisting with type 1 VWD, characterized by VWF gene conversion variants (p.V1229G and p.N1231T) and a heterozygous missense mutation p.R2118W, along with an intron 22 inversion in the F8 gene. These gene conversion variants are rarely reported in China. These findings provide insights into the molecular pathogenesis of combined VWD and hemophilia A.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"220-227"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombin generation profiling in multiple myeloma: a comprehensive evaluation of prothrombotic state.","authors":"Ciro Miele, Alessandra Vasco, Luca Manfredi, Immacolata Randa, Roberta Della Pepa, Stella Puzone, Raffaella Addesso, Vittoria Di Vico, Nadia Tinto, Giulia Frisso, Olga Scudiero, Savoia Marcella, Cristina Mazzaccara","doi":"10.1097/MBC.0000000000001424","DOIUrl":"10.1097/MBC.0000000000001424","url":null,"abstract":"<p><strong>Objective: </strong>Venous thromboembolism is a major complication in patients with multiple myeloma (MM), with treatment strategies further increasing thrombotic risk. Conventional coagulation tests (CCT) fail to reflect the in vivo hemostatic balance, whereas thrombin generation assay (TGA) provides a global assessment of thrombin dynamics and may better identify hypercoagulable states in MM.</p><p><strong>Methods: </strong>To this aim, to evaluated thrombin generation, we enrolled 20 MM patients during follow-up while receiving active MM-treatment: sixteen had immunoglobulin G (IgG) MM, one immunoglobulin A (IgA) MM, one light-chain MM, and two biclonal MM (IgG and IgA). Citrated blood samples were collected under standardized conditions for CCT and TGA. Thrombin generation was measured in platelet poor plasma, both in the absence and presence of thrombomodulin (TM) using the ST Genesia system.</p><p><strong>Results: </strong>TGA revealed increased peak height (139.75%; r.v. 40-69%), endogenous thrombin potential (107.80%; r.v. 58-78%), and velocity index (153.10%; r.v. 31-62%), along with shortened time to peak (ratio 1.04; r.v. 1.2-1.5). Notably, TM-mediated inhibition of thrombin generation was reduced (16.20%; r.v. 60-76%), indicating protein C pathway dysfunction despite preserved natural anticoagulant levels. This procoagulant state was further supported by elevated fibrinogen and D-dimer, together with increased factor VIII and von Willebrand levels.</p><p><strong>Conclusion: </strong>Our findings confirm a hypercoagulable state in MM patients, likely related to endothelial injury and systemic inflammation. Impairment of the protein C pathway, as highlighted by TGA, further contributes to this imbalance. In light of the limitations of prothrombin time and activated partial thromboplastin time, TGA provides a more sensitive and informative evaluation of coagulation dynamics in MM patients.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"161-167"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant ADAMTS13 in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.","authors":"Anaya Abdul Samad, Safwat Irshad Qureshi, Akif Shahid Khan, Bilal Khan, Muhammad Tufail, Nourhan Saeed Bakry","doi":"10.1097/MBC.0000000000001423","DOIUrl":"10.1097/MBC.0000000000001423","url":null,"abstract":"<p><strong>Objective: </strong>Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal blood disorder due to deficiency of the enzyme ADAMTS13. Recombinant ADAMTS13 (rADAMTS13) is a new treatment aimed at restoring enzyme activity. This study aimed to evaluate the efficacy and safety of rADAMTS13 compared to standard therapy or placebo in patients with congenital or acquired TTP using a systematic review and meta-analysis.</p><p><strong>Methods: </strong>This PRISMA-compliant review searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and others up to March 30, 2025. We included randomized controlled trials (RCTs) comparing rADAMTS13 to standard therapy or placebo in patients with TTP.</p><p><strong>Results: </strong>Two RCTs (one phase 3, one phase 2) involving 129 patients (67 rADAMTS13, 62 placebo) met inclusion criteria. No significant differences were observed for the primary clinical outcomes of acute TTP events (risk ratio (RR) = 0.58 [95% CI, 0.20-1.70]) or serious treatment-emergent adverse events (RR = 0.64 [95% CI, 0.31-1.34]). However, rADAMTS13 significantly increased ADAMTS13 activity levels (MD, 0.92 IU/ml [95% CI, 0.59-1.26]; P  < 0.0001). Urticaria was significantly lower in the rADAMTS13 group (RR = 0.25 [95% CI, 0.06-0.96]; P  = 0.04). No significant differences were noted for other adverse events (all P > 0.05).</p><p><strong>Conclusion: </strong>rADAMTS13 significantly enhances ADAMTS13 activity but did not demonstrate a significant improvement in key clinical outcomes. These findings, based on two RCTs, are of moderate to low certainty per GRADE assessment. Larger trials are needed to confirm the clinical benefits of rADAMTS13.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"140-150"},"PeriodicalIF":1.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance evaluation of Stago sthemO 301 hemostasis analyzer for routine testing, coagulation factors, and inhibitors.","authors":"Marjorie A Goujon, Nicole Pesnel, Joffrey Feriel, Véronique Le Cam Duchez, Frank Mentz, Françoise Le Boulaire, Romain Duriez, Bas De Laat, Emmanuel de Maistre, Aurélien Lebreton","doi":"10.1097/MBC.0000000000001421","DOIUrl":"10.1097/MBC.0000000000001421","url":null,"abstract":"<p><p>The sthemO 301 is a new hemostasis analyzer developed by Diagnostica Stago, combining simultaneously three different methodologies (i.e. clotting, chromogenic and immunological assays) on a single platform. The objective of this evaluation was to assess the analytical performances of the sthemO 301 and to compare it with the STA R Max on a selection of 20 hemostasis parameters (PT, aPTT with two reagents, Clauss fibrinogen, thrombin time, D-dimer, anti-Xa, factors II, V, VII, X, VIII, IX and XI, antithrombin, protein C and protein S). Within-run and inter-laboratory precisions have been evaluated using quality controls. Method comparisons were performed using a minimum of 100 plasma samples, collected across multiple sites, and compared to the STA R Max analyzer. Reference intervals were determined or verified based on published data. Within-run and inter-laboratory precisions were respectively below 5.2 and 7.6% whatever the parameter and the sample used. Pearson correlation coefficient was above 0.976 for all assays and slopes ranged from 0.94 to 1.07 for all but thrombin time, which was at 0.86. Bias at levels of interest were less than 6% for most routine coagulation parameters, coagulation factors and inhibitors. We reported the precision, accuracy and reference intervals of 20 parameters on the sthemO 301, half of these being reported for the first time, which include anti-Xa, factors II, V, VII, X, VIII, IX, XI, protein S free antigen and activity. The sthemO 301 analyzer offers satisfactory analytical performance and a good comparability with the STA R Max for all parameters.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"151-160"},"PeriodicalIF":1.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FIXa-triggered thrombin generation correlates with FVIII levels less than 1% in reconstituted plasma mimicking samples obtained from patients with severe hemophilia A.","authors":"Meijuan Huang, Jorell Gantioqui, Anthony K C Chan, Howard H W Chan","doi":"10.1097/MBC.0000000000001422","DOIUrl":"10.1097/MBC.0000000000001422","url":null,"abstract":"<p><strong>Introduction: </strong>More than 10% of severe hemophilia A patients are paradoxically mild bleeders despite factor VIII (FVIII) levels being <1 IU/dl. Quantitation of FVIII levels <1 IU/dl is a challenge due to the detection limits of traditional one-stage activated partial thromboplastin time, two-stage chromogenic assay, and tissue factor-initiated thrombin generation assay (TF-TGA), impeding a precise characterization of the bleeding phenotype in severe hemophilia patients.</p><p><strong>Objective: </strong>The study aimed to enhance the sensitivity of TGA by modifying the trigger reagent for FVIII measurement.</p><p><strong>Methodology: </strong>We optimized the fluorometric quantitation of thrombin generation triggered by factor IXa (FIXa) in artificial reconstituted plasma by blending varying proportions of normal pooled plasma (NPP) and FVIII-immunodepleted plasma containing a normal level of von Willebrand factor.</p><p><strong>Results: </strong>FIXa-initiated thrombin generation depended on FVIII level, while TF could bypass FVIII deficiency to activate thrombin, making TF-TGA incapable of quantifying low levels of FVIII. When triggering with 0.6 nM FIXa, in the presence of 4 μM phospholipids and 40 μg/ml corn trypsin inhibitor, thrombin generation was highly dependent on FVIII levels even below 1 IU/dl. Among the five routinely used TGA parameters, peak thrombin, endogenous thrombin potential, and velocity index demonstrated the strongest linear correlation with FVIII levels down to 0.1 IU/dl.</p><p><strong>Conclusion: </strong>The study evaluated the performance of a modified TGA activated with FIXa. In addition to traditional TF-TGA, FIXa-TGA may provide additional information when assessing the bleeding tendency of patients with severe hemophilia A, facilitating personalized factor replacement therapy.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"133-139"},"PeriodicalIF":1.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147477741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}